Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

Jaffar, J; Unger, S; Corte, TJ; Keller, M; Wolters, PJ; Richeldi, L; Cerri, S; Prêle, CM; Hansbro, PM; Argraves, WS; Oliver, RA; Oliver, BG; Black, JL; Burgess, JK

Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

Jaffar, J Unger, S Corte, TJ Keller, M Wolters, PJ Richeldi, L Cerri, S Prêle, CM Hansbro, PM Argraves, WS Oliver, RA Oliver, BG Black, JL Burgess, JK

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Publisher:: American College of Chest Physicans
Publication Type:: Journal Article
Citation:: Chest, 2014, 146, (4), pp. 1055-1063
Issue Date:: 2014-01

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Field	Value	Language
dc.contributor.author	Jaffar, J
dc.contributor.author	Unger, S
dc.contributor.author	Corte, TJ
dc.contributor.author	Keller, M
dc.contributor.author	Wolters, PJ
dc.contributor.author	Richeldi, L
dc.contributor.author	Cerri, S
dc.contributor.author	Prêle, CM
dc.contributor.author	Hansbro, PM
dc.contributor.author	Argraves, WS
dc.contributor.author	Oliver, RA
dc.contributor.author	Oliver, BG
dc.contributor.author	Black, JL
dc.contributor.author	Burgess, JK
dc.date.accessioned	2021-03-03T23:19:52Z
dc.date.available	2021-03-03T23:19:52Z
dc.date.issued	2014-01
dc.identifier.citation	Chest, 2014, 146, (4), pp. 1055-1063
dc.identifier.issn	0012-3692
dc.identifier.issn	1931-3543
dc.identifier.uri	http://hdl.handle.net/10453/146731
dc.description.abstract	Background The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells, thus may contribute to lung fibrosis in IPF. Methods Serum, lung tissue and lung function values were obtained from four independent locations (Sydney and Perth, Australia, San Francisco, USA and Modena, Italy). Patients with IPF were followed for a minimum of one year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under non-stimulatory conditions. Fibulin-1 levels in serum and secreted or deposited by fibroblasts were measured by western blot and in lung tissue by immunohistochemistry. Results Serum fibulin-1 levels were increased in patients with IPF compared to subjects without lung disease (p=0.006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (p=0.02) and correlated negatively with lung function (r=-0.9, p<0.05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (p<0.05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (AUC 0.71, 95%CI 0.57 0.86, p=0.012). Conclusions Fibulin-1 is a novel potential biomarker for disease progression IPF and raise the possibility that it could be used as a target for the development of new treatments.
dc.format	Print
dc.language	eng
dc.publisher	American College of Chest Physicans
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1026880
dc.relation.ispartof	Chest
dc.relation.isbasedon	10.1378/chest.13-2688
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences
dc.subject.classification	Respiratory System
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Humans
dc.subject.mesh	Disease Progression
dc.subject.mesh	Calcium-Binding Proteins
dc.subject.mesh	Blotting, Western
dc.subject.mesh	Cell Culture Techniques
dc.subject.mesh	Immunohistochemistry
dc.subject.mesh	Follow-Up Studies
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Middle Aged
dc.subject.mesh	United States
dc.subject.mesh	Australia
dc.subject.mesh	Italy
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Idiopathic Pulmonary Fibrosis
dc.subject.mesh	Biomarkers
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Australia
dc.subject.mesh	Biomarkers
dc.subject.mesh	Blotting, Western
dc.subject.mesh	Calcium-Binding Proteins
dc.subject.mesh	Cell Culture Techniques
dc.subject.mesh	Disease Progression
dc.subject.mesh	Female
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Follow-Up Studies
dc.subject.mesh	Humans
dc.subject.mesh	Idiopathic Pulmonary Fibrosis
dc.subject.mesh	Immunohistochemistry
dc.subject.mesh	Italy
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	United States
dc.title	Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.
dc.type	Journal Article
utslib.citation.volume	146
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1103 Clinical Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2021-03-03T23:19:50Z
pubs.issue	4
pubs.publication-status	Published
pubs.volume	146
utslib.citation.issue	4

Abstract:

Background The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells, thus may contribute to lung fibrosis in IPF. Methods Serum, lung tissue and lung function values were obtained from four independent locations (Sydney and Perth, Australia, San Francisco, USA and Modena, Italy). Patients with IPF were followed for a minimum of one year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under non-stimulatory conditions. Fibulin-1 levels in serum and secreted or deposited by fibroblasts were measured by western blot and in lung tissue by immunohistochemistry. Results Serum fibulin-1 levels were increased in patients with IPF compared to subjects without lung disease (p=0.006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (p=0.02) and correlated negatively with lung function (r=-0.9, p<0.05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (p<0.05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (AUC 0.71, 95%CI 0.57 0.86, p=0.012). Conclusions Fibulin-1 is a novel potential biomarker for disease progression IPF and raise the possibility that it could be used as a target for the development of new treatments.

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http://hdl.handle.net/10453/146731